Adiponectin and AMP kinase activator stimulate proliferation, differentiation, and mineralization of osteoblastic MC3T3-E1 cells

<p>Abstract</p> <p>Background</p> <p>Adiponectin is a key mediator of the metabolic syndrome that is caused by visceral fat accumulation. Adiponectin and its receptors are known to be expressed in osteoblasts, but their actions with regard to bone metabolism are still unclear. In this study, we investigated the effects of adiponectin on the proliferation, differentiation, and mineralization of osteoblastic MC3T3-E1 cells.</p> <p>Results</p> <p>Adiponectin receptor type 1 (AdipoR1) mRNA was detected in the cells by RT-PCR. The adenosine monophosphate-activated protein kinase (AMP kinase) was phosphorylated by both adiponectin and a pharmacological AMP kinase activator, 5-amino-imidazole-4-carboxamide-riboside (AICAR), in the cells. AdipoR1 small interfering RNA (siRNA) transfection potently knocked down the receptor mRNA, and the effect of this knockdown persisted for as long as 10 days after the transfection. The transfected cells showed decreased expressions of type I collagen and osteocalcin mRNA, as determined by real-time PCR, and reduced ALP activity and mineralization, as determined by von Kossa and Alizarin red stainings. In contrast, AMP kinase activation by AICAR (0.01–0.5 mM) in wild-type MC3T3-E1 cells augmented their proliferation, differentiation, and mineralization. BrdU assay showed that the addition of adiponectin (0.01–1.0 μg/ml) also promoted their proliferation. Osterix, but not Runx-2, appeared to be involved in these processes because AdipoR1 siRNA transfection and AICAR treatments suppressed and enhanced osterix mRNA expression, respectively.</p> <p>Conclusion</p> <p>Taken together, this study suggests that adiponectin stimulates the proliferation, differentiation, and mineralization of osteoblasts via the AdipoR1 and AMP kinase signaling pathways in autocrine and/or paracrine fashions.</p

Production of Low-Potassium Content Melon Through Hydroponic Nutrient Management Using Perlite Substrate

Chronic kidney disease patients are restricted to foods with high potassium content but our daily diets including melon are rich in potassium. Therefore, we investigated the production of low-potassium melon through hydroponic nutrient management in soilless culture using perlite substrate during autumn season of 2012, 2014 and spring season of 2016. In the first study, melon plants were supplied with 50% standard ‘Enshi’ nutrient solution until first 2 weeks of culture. In 3rd and 4th week, amount of applied potassium was 50, 75, 100, and 125% of required potassium nitrate for each plant per week (based on our previous study). It was found that, melon plants grown with 50% of its required potassium nitrate produced fruits with about 53% low-potassium compared to control. In the following study, four cultivars viz. Panna, Miyabi shunjuukei, Miyabi akifuyu412, and Miyabi soushun banshun309 were evaluated for their relative suitability of low-potassium melon production. Results showed insignificant difference in fruit potassium content among the cultivars used. Source of potassium fertilizer as potassium nitrate and potassium sulfate and their restriction (from 1 or 2 weeks after anthesis) were also studied. There were no influences on fruit potassium content and yield due to sources of potassium fertilizer and restriction timings. In our previous studies, it was evident that potassium can be translocated from leaves to fruits at maturity when it was supplied nutrient without potassium. Thus, we also studied total number of leaves per plant (23, 24, 25, 26, and 27 leaves per plant). It was evident that fruit potassium, yield, and quality were not influenced significantly due to differences in number of leaves per plant. These studies showed that restriction of potassium nitrate in the culture solution from anthesis to harvest could produce melon fruits with low-potassium (&gt;20%) content compared to potassium content of greenhouse grown melon (340 mg/100 g FW). Quality testing and clinical validation of low-potassium melon also showed positive responses compared to greenhouse grown melon

The calcium-sensing receptor and calcimimetics in blood pressure modulation

Calcium is a crucial second messenger in the cardiovascular system. However, calcium may also be an extracellular first messenger through a G-protein-coupled receptor that senses extracellular concentration (Ca(2+)(o)), the calcium-sensing receptor (CaR). The most prominent physiological function of the CaR is to maintain the extracellular Ca(2+) level in a very tight range by regulating the circulating levels of parathyroid hormone (PTH). This control over PTH and Ca(2+) levels is partially lost in patients suffering from primary and secondary hyperparathyroidism. Allosteric modulators of the CaR (calcimimetics) are the first drugs in their class to become available for clinical use and have been shown to successfully treat certain forms of primary and secondary hyperparathyroidism. In addition, several studies suggest beneficial effects of calcimimetics on cardiovascular risk factors associated with hyperparathyroidism. Although a plethora of studies demonstrated the CaR in heart and blood vessels, exact roles of the receptor in the cardiovascular system still remain to be elucidated. However, several studies point toward a possibility that the CaR might be involved in the regulation of vascular tone. This review will summarize the current knowledge on the possible functions of the CaR and calcimimetics on blood pressure regulation. LINKED ARTICLES: This article is part of a themed issue on Vascular Endothelium in Health and Disease. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.164.issue-

The Role of the Vascular System in Degenerative Diseases: Mechanisms and Implications

Degenerative diseases, encompassing a wide range of conditions affecting various organ systems, pose significant challenges to global healthcare systems. This comprehensive review explores the intricate interplay between the vascular system and degenerative diseases, shedding light on the underlying mechanisms and profound implications for disease progression and management. The pivotal role of the vascular system in maintaining tissue homeostasis is highlighted, as it serves as the conduit for oxygen, nutrients, and immune cells to vital organs and tissues. Due to the vital role of the vascular system in maintaining homeostasis, its dysfunction, characterized by impaired blood flow, endothelial dysfunction, and vascular inflammation, emerges as a common denominator of degenerative diseases across multiple systems. In the nervous system, we explored the influence of vascular factors on neurodegenerative diseases such as Alzheimer’s and Parkinson’s, emphasizing the critical role of cerebral blood flow regulation and the blood–brain barrier. Within the kidney system, the intricate relationship between vascular health and chronic kidney disease is scrutinized, unraveling the mechanisms by which hypertension and other vascular factors contribute to renal dysfunction. Throughout this review, we emphasize the clinical significance of understanding vascular involvement in degenerative diseases and potential therapeutic interventions targeting vascular health, highlighting emerging treatments and prevention strategies. In conclusion, a profound appreciation of the role of the vascular system in degenerative diseases is essential for advancing our understanding of degenerative disease pathogenesis and developing innovative approaches for prevention and treatment. This review provides a comprehensive foundation for researchers, clinicians, and policymakers seeking to address the intricate relationship between vascular health and degenerative diseases in pursuit of improved patient outcomes and enhanced public health

Changes in the Urinary Sodium-to-Potassium Ratio Are Associated with Blood Pressure Change in Older Japanese Adults : A 7-Year Longitudinal Study

Studies on the association between sodium-to-potassium (Na/K) ratio changes and blood pressure (BP) changes among older adults are limited. This 7-year longitudinal study examined the association between Na/K ratio changes (evaluated using spot urine tests) and BP changes among older Japanese adults. Data were collected from 432 participants (mean age: 70.3±4.4; range: 65–84 years) in 2012 and 2019. Changes in BP and the Na/K ratio over 7 years were calculated by subtracting baseline values from values noted during a follow-up survey. The median systolic and diastolic BP (SBP) and (DBP) changes after 7 years were 4 (IQR, −7, 14) and −1 (IQR, −9, 5) mmHg, respectively. The median Na/K ratio was changed during the follow-up period by −0.2 (IQR, −1.3, 0.7). A generalized linear model indicated that Na/K ratio changes were positively associated with SBP (B = 2.03, p < 0.001) and DBP (B = 0.62, p = 0.021) changes. In the non-antihypertensive medication-using group, urinary Na/K ratio changes were associated with SBP and DBP changes (B = 2.39, p = 0.001; B = 0.99, p = 0.033). In the antihypertensive medication user group, urinary Na/K ratio changes were associated with SBP changes (B = 1.62, p = 0.015). We confirmed the association between changes in the Na/K ratio and changes in BP

Neighborhood environment and muscle mass and function among rural older adults : a 3-year longitudinal study

Background: Sarcopenia, resulting from loss of muscle mass and function, is highly prevalent in the ageing societies and is associated with risk of falls, frailty, loss of independence, and mortality. It is important to identify environmental risk factors, so that evidence-based interventions to prevent sarcopenia can be implemented at the population level. This study aimed to examine the potential effect of several objectively measured neighborhood environmental factors on longitudinal change of muscle mass and function among older adults living in rural Japanese towns where the population is ageing. Methods: This study was based on data from the Shimane CoHRE Study conducted by the Center for Community-based Healthcare Research and Education (CoHRE) at Shimane University in 3 rural towns in the Shimane Prefecture, Japan. Subjects older than 60 years, who participated in an annual health examination in 2016 and any follow-up years until 2019, i.e., 4 possible time points in total, were included (n = 2526). The skeletal muscle mass index (SMI) and grip strength were assessed objectively for each year as a measure of muscle mass and function, respectively. Neighborhood environmental factors, i.e., hilliness, bus stop density, intersection density, residential density, and distance to a community center were measured by geographic information systems (GIS). Linear mixed models were applied to examine the potential effect of each neighborhood environmental factor on the change of SMI and grip strength over time. Results: Males living far from community centers had a less pronounced decline in SMI compared to those living close to community centers. Females living in areas with higher residential density had a less pronounced decline in grip strength compared to those living in areas with lower residential density. Conclusions: Neighborhood environmental factors had limited effects on change of SMI and grip strength among rural older adults within the 3 years follow up. Further long-term follow up studies are necessary by also taking into account other modifiable neighborhood environmental factors